In 2269, Kirk argued in favor of having Sargon and his companions take over the bodies of the crew, and emphasized the benefits that it might possibly have on mankind, he explained, "they used to say if man could fly, he'd have wings. But he did fly. He discovered he had to. Do you wish that the first Apollo mission hadn't reached the moon or that we hadn't gone on to Mars or the nearest star?" (TOS: "Return to Tomorrow")

In another alternate timeline, the Xindi destroyed all Human outposts they could find, after destroying Earth, including the ones located on Mars, Alpha Centauri and Vega colony in 2154. (ENT: "Twilight")

The association of Alpha Centauri as the fifth founding member was also referenced in the "It's Federation Day!" newspaper article, created as background material for Star Trek Generations. According to that article, Alpha Centauri had recently gained its independence. Titus Cleet, who signed the founding document of the Federation, was the system's ambassador.

According to Star Trek: Star Charts (pgs. 19, 36, 45, "United Federation of Planets I", "United Federation of Planets IV"), in the early 22nd century, an Earth colony was founded on a M-class world in this system. This world had the same name as the system. In 2120, Zefram Cochrane departed from Alpha Centauri on his final voyage. In the mid-22nd century, Alpha Centauri was a destination on the Earth trade routes. The colony traded with Earth and Vulcan. Alpha Centauri became a Federation founding member in 2161. In 2378, Alpha Centauri was a member planet. The Alpha Centauri system was located in or near Federation space. Alpha Centauri A was a G-class star with a magnitude of +5, which was the same brightness of Sol. Alpha Centauri B was a K-class star. This system was located in Sector 002 also known as the Alpha Centauri sector, the second sector to be explored by Earth ships.

The chart naming stars within 20 light years of Sol was originally drawn by Rick Sternbach for the Star Trek Spaceflight Chronology in the late 1970s. Found on page 77, this chart showed Earth commercial and exploration routes after the use of warp drive began. Alpha Centauri was the terminus for two major commerical routes, Epsilon Eridani-Alpha Centauri and Sol-Alpha Centauri.

Alpha Centauri was misspelled as "Alpha Centuri" in the "The Explored Galaxy" star chart graphic seen in Star Trek: The Undiscovered Country.

In the real world, in 2012, astronomers announced the discovery of Alpha Centauri Bb. This extrasolar planet, unconfirmed as of 2014, might be a Earth-size terrestrial planet. Attempts to locate other planets in the Alpha Centauri system have been, to date, unsuccessful.

According to the PC CD-ROM game Star Trek: 25th Anniversary, the 2160s-era Cochrane-500 Fusion Drive was manufactured on Alpha Centauri. These engines were well made and still in use a century later.

In the FASArole playing game the Alpha Centaurians were the first extraterrestrial civilization Humans encounter. The historic meeting occurred in 2042 when the Earth's United Nations space craft, the UNSS Icarus, utilizing a Bussard collector, arrived in the Alpha Centauri system. In 2048, Zefram Cochrane, an Alpha Centarian, sent his warp drive discovery to Earth. This contrasts with Star Trekcanon material, which establishes that Cochrane was an Earth-born Human.

Like in the FASA game, the Last Unicorn role playing game and the Decipher RPG, Alpha Centauri was already inhabited by a humanoid species when Terran explorers first ventured there in 2066. The Terrans traded their warp drive technology for Centaurian terraforming technology, to repair Earth's shattered ecosystem in the aftermath of World War III.